| Size | Price | Stock | Qty |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Asperosaponin VI modulates multiple signaling pathways and targets a diverse range of proteins. Its primary targets include Caspase 3, PERK, p38 MAPK, Akt, HIF/HIF Prolyl-Hydroxylase, and PPAR. The compound induces osteoblast differentiation through the BMP-2/p38 and ERK1/2 signaling pathways, promoting bone formation. It protects against hypoxia-induced cardiomyocyte apoptosis by activating the PI3K/Akt and CREB pathways. In chondrocytes, Asperosaponin VI exerts protective effects by modulating the AMPK-SIRT3 pathway to mitigate mitochondrial dysfunction and endoplasmic reticulum stress. Additionally, it suppresses ferroptosis in chondrocytes through the Nrf2/GPX4/HO-1 signaling pathway, thereby ameliorating osteoarthritis. The compound also demonstrates the ability to prevent lipid accumulation in hepatocytes via activation of AMPK and down-regulation of lipogenic genes.
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| ln Vitro |
In vitro studies have demonstrated that Asperosaponin VI (0.1 nM-10 μM; 24-48 hours) significantly promotes the proliferation of MC3T3-E1 cells and primary rat osteoblasts. It increases intracellular alkaline phosphatase (ALP) activity, upregulates BMP-2 protein levels, and enhances the phosphorylation of p38 and ERK1/2 to induce osteoblast maturation and differentiation. In hypoxia-treated H9C2 cardiomyocytes, Asperosaponin VI (15-60 μg/mL; 24 hours) inhibits apoptosis and improves cell viability by reducing intracellular lactate dehydrogenase (LDH) and creatine kinase (CK) activities, increasing the phosphorylation levels of Akt and CREB, elevating the Bcl-2/Bax ratio, and decreasing active caspase-3 expression. In TBHP-treated chondrocytes, Asperosaponin VI significantly enhances cell viability, reduces apoptosis, and mitigates extracellular matrix degradation and mitochondrial dysfunction. It also suppresses ferroptosis in chondrocytes. The compound has been shown to reduce intracellular reactive oxygen species and increase the proportion of cells in the S phase under hypoxic conditions. CCK-8 assays have confirmed that Asperosaponin VI at concentrations up to 2 μM does not affect cell viability after 1, 4, or 7 days of culture.
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| ln Vivo |
In vivo, Asperosaponin VI has demonstrated significant therapeutic potential in various animal models. In models of osteoporosis, it induces osteoblast maturation and differentiation, thereby increasing bone formation. In osteoarthritis models, it ameliorates disease progression by modulating the AMPK-SIRT3 pathway, addressing ER stress, mitochondrial dysfunction, and chondrocyte apoptosis. The compound also suppresses ferroptosis in chondrocytes and ameliorates osteoarthritis through the Nrf2/GPX4/HO-1 signaling pathway. In cardiac injury models, Asperosaponin VI protects against hypoxia-induced cardiomyocyte apoptosis. Additionally, it exhibits antidepressant and wound-healing-promoting activities in preclinical studies. However, the in vivo efficacy of Asperosaponin VI is severely limited by its poor oral bioavailability (<0.13%). Recent studies have shown that the compound can spontaneously form dynamic self-assembled structures with sodium taurocholate (NaTC) and dipalmitoyl phosphatidylcholine (DOPC) during gastrointestinal solubilization, which promotes its gastrointestinal absorption and permeability and increases its in vivo exposure.
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| Enzyme Assay |
For non-cellular enzyme/receptor binding assays, Asperosaponin VI can be evaluated using a variety of biochemical techniques. Kinase activity assays using purified enzyme preparations can be employed to assess the compound's modulation of p38 MAPK, ERK1/2, Akt, and other kinase targets. The activation or inhibition of these enzymes can be measured using standard radioactive or luminescent kinase activity detection methods with varying concentrations of the compound. For apoptosis-related targets such as Caspase 3, fluorometric or colorimetric substrate cleavage assays can be used to determine the compound's inhibitory effects. The binding affinity of Asperosaponin VI to transcription factors such as PPAR can be assessed using fluorescence polarization or surface plasmon resonance (SPR) techniques. For studies involving the AMPK-SIRT3 pathway, enzyme activity assays using purified AMPK and SIRT3 proteins can be conducted to measure direct activation or inhibition. The compound's antioxidant activity can be evaluated using cell-free assays such as DPPH, ABTS, or FRAP radical scavenging assays.
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| Cell Assay |
For in vitro cell-based assays, a variety of cell culture models have been established to evaluate the biological activities of Asperosaponin VI. For osteoblast differentiation studies, MC3T3-E1 cells and primary rat osteoblasts are cultured in appropriate media and treated with Asperosaponin VI at concentrations ranging from 0.1 nM to 10 μM for 24-48 hours. Cell proliferation is assessed using CCK-8 or MTT assays. Alkaline phosphatase (ALP) activity is measured using colorimetric assays, and mineralization is evaluated by Alizarin Red S staining. Protein expression of BMP-2, phosphorylated p38, and ERK1/2 is analyzed by Western blotting. For cardiomyocyte protection studies, H9C2 cells are subjected to hypoxia and treated with Asperosaponin VI (15-60 μg/mL; 24 hours). Cell viability is assessed, and intracellular LDH and CK activities are measured. Apoptosis is evaluated by flow cytometry using Annexin V/PI staining, and the expression of Bcl-2, Bax, and cleaved caspase-3 is analyzed by Western blotting. For chondrocyte studies, primary chondrocytes are treated with TBHP to induce oxidative stress, and the protective effects of Asperosaponin VI are evaluated by measuring cell viability, apoptosis, and extracellular matrix degradation.
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| Animal Protocol |
For in vivo animal studies, Asperosaponin VI has been evaluated in various disease models. In osteoporosis models, the compound is typically administered orally or intraperitoneally to rodents, and bone formation is assessed by measuring bone mineral density, histomorphometry, and serum markers of bone turnover. In osteoarthritis models, Asperosaponin VI is administered to mice or rats, and disease progression is evaluated by histological analysis of cartilage degradation, subchondral bone changes, and synovial inflammation. The compound's effects on chondrocyte apoptosis, extracellular matrix metabolism, and inflammatory markers are assessed. In cardiac injury models, the compound's cardioprotective effects are evaluated by measuring cardiac function, infarct size, and biomarkers of cardiac injury. For pharmacokinetic studies, the compound is administered to rats via oral gavage or intravenous injection, and plasma concentrations are measured using HPLC or LC-MS/MS. The absorption mechanism can be investigated using quadruple single-pass intestinal perfusion in rats.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Asperosaponin VI are characterized by its BCS class III classification (high solubility, low permeability). The compound exhibits extremely poor oral bioavailability, reported to be less than 0.13%. It is highly hydrophilic, which contributes to its limited gastrointestinal absorption. In vitro solubility studies show that Asperosaponin VI is soluble in water at 100 mg/mL (107.63 mM) and in DMSO at ≥25 mg/mL (26.91 mM). For in vivo administration, the compound can be formulated using various solvent systems: PBS (25 mg/mL, clear solution), 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline (≥2.5 mg/mL), 10% DMSO + 90% (20% SBE-β-CD in saline) (≥2.5 mg/mL), or 10% DMSO + 90% corn oil (≥2.5 mg/mL). The powder should be stored at -20°C, protected from light, and in solvent at -80°C for 6 months or at -20°C for 1 month. Recent studies have demonstrated that Asperosaponin VI can spontaneously form dynamic self-assembled nanostructures with endogenous gastrointestinal components (NaTC and DOPC), which significantly promotes its gastrointestinal absorption and permeability and increases its in vivo exposure. These self-assembled nanostructures exhibit higher cellular uptake in Caco-2 cells as evidenced by flow cytometry and confocal microscopy.
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| Toxicity/Toxicokinetics |
The toxicological profile of Asperosaponin VI has been evaluated in preclinical studies. As a natural saponin component from a medicinal herb traditionally used as an anti-osteoporosis drug, the compound is generally considered to have a favorable safety profile at therapeutic doses. In vitro studies have shown that Asperosaponin VI at concentrations up to 2 μM does not affect cell viability after 1, 4, or 7 days of culture. However, as with many saponins, higher concentrations may cause hemolytic effects or gastrointestinal irritation. The compound's poor oral bioavailability (<0.13%) may limit systemic exposure and reduce the risk of off-target toxicity. No significant acute or chronic toxicity has been reported in the available literature. The compound's safety in humans has not been fully established, and it is intended for research use only.
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| References |
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| Additional Infomation |
Akebia saponin D is a triterpenoid saponin with the structure of ipogoninogen linked by a glycosidic bond to an α-L-arabinopyranose residue at position 3 and by an ester bond to a 6-O-β-D-glucopyranosyl-β-D-glucopyranose residue at position 28. It is the active ingredient of the traditional Chinese medicine Forsythia suspensa. It possesses various effects including inducing apoptosis, antitumor activity, plant metabolism regulation, anti-inflammation, maintaining bone density, neuroprotection, and lowering blood lipids. It is a triterpenoid saponin, a trisaccharide derivative, a pentacyclic triterpenoid compound, and a carboxylic acid ester. Its function is related to ipogoninogen. Akebia saponin VI has also been reported in honeysuckle, alfalfa, and other organisms with relevant data.
Asperosaponin VI is also known by the aliases Akebia saponin D (ASD) and ASA VI. It is the principal pharmacologically active marker and quality control index for Dipsacus asper Wall (Dipsaci Radix), a traditional medicinal herb. The compound's diverse pharmacological activities include osteoprotective, cardioprotective, antidepressant, and wound-healing-promoting effects. Its mechanism of action involves the modulation of multiple signaling pathways, including BMP-2/p38, ERK1/2, PI3K/Akt, CREB, AMPK-SIRT3, and Nrf2/GPX4/HO-1. Despite its promising biological activities, the compound's clinical development is significantly hindered by its extremely low oral bioavailability. Recent research has focused on overcoming this limitation through innovative formulation strategies, including the development of dynamic self-assembled nanostructures with endogenous gastrointestinal components to enhance absorption and in vivo exposure. The compound is not currently approved for clinical use and is available only for research purposes. |
| Molecular Formula |
C47H76O18
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|---|---|
| Molecular Weight |
929.0956
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| Exact Mass |
928.503
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| CAS # |
39524-08-8
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| PubChem CID |
14284436
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| Appearance |
White to off-white solid powder
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| Density |
1.43
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| Boiling Point |
990.2±65.0 °C at 760 mmHg
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| Flash Point |
282.1±27.8 °C
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| Vapour Pressure |
0.0±0.6 mmHg at 25°C
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| Index of Refraction |
1.627
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| LogP |
4.18
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| Hydrogen Bond Donor Count |
11
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| Hydrogen Bond Acceptor Count |
18
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
65
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| Complexity |
1770
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| Defined Atom Stereocenter Count |
23
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| SMILES |
C[C@]12CC[C@@H]([C@@]([C@@H]1CC[C@@]3([C@@H]2CC=C4[C@]3(CC[C@@]5([C@H]4CC(CC5)(C)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO[C@H]7[C@@H]([C@H]([C@@H]([C@H](O7)CO)O)O)O)O)O)O)C)C)(C)CO)O[C@H]8[C@@H]([C@H]([C@H](CO8)O)O)O
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| InChi Key |
CCRXMHCQWYVXTE-HMRSNRLKSA-N
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| InChi Code |
InChI=1S/C47H76O18/c1-42(2)13-15-47(41(59)65-40-37(58)34(55)32(53)26(63-40)20-61-38-36(57)33(54)31(52)25(18-48)62-38)16-14-45(5)22(23(47)17-42)7-8-28-43(3)11-10-29(64-39-35(56)30(51)24(50)19-60-39)44(4,21-49)27(43)9-12-46(28,45)6/h7,23-40,48-58H,8-21H2,1-6H3/t23-,24-,25+,26+,27+,28+,29-,30-,31+,32+,33-,34-,35+,36+,37+,38+,39-,40-,43-,44-,45+,46+,47-/m0/s1
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| Chemical Name |
[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl] (4aS,6aR,6aS,6bR,8aR,9R,10S,12aR,14bS)-9-(hydroxymethyl)-2,2,6a,6b,9,12a-hexamethyl-10-[(2S,3R,4S,5S)-3,4,5-trihydroxyoxan-2-yl]oxy-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~100 mg/mL (~107.63 mM)
DMSO : ≥ 25 mg/mL (~26.91 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (2.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 25 mg/mL (26.91 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0763 mL | 5.3816 mL | 10.7631 mL | |
| 5 mM | 0.2153 mL | 1.0763 mL | 2.1526 mL | |
| 10 mM | 0.1076 mL | 0.5382 mL | 1.0763 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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